ATCT-07PHASE 2 STUDY OF MEDI-575, AN ANTI-PLATELET-DERIVED GROWTH FACTOR-α ANTIBODY, IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Altered expression of platelet-derived growth factor-α (PDGF-α) and of the PDGF-α receptor (PDGFR-α) has been implicated in the development of glioblastoma (GB). MEDI-575, an immunoglobulin G2κ (IgG2κ) monoclonal antibody, selectively binds to PDGFR-α with high specificity, without cross-reacting with the PDGF-β receptor. METHODS: A phase 2, multicenter, single-arm, open-label study evaluated the efficacy and safety of MEDI-575 in patients with recurrent GB. Adults with a first recurrence following surgery, temozolomide, and radiation therapy were eligible. Patients received MEDI-575 25 mg/kg intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity. The primary end point was 6-month progression-free survival (PFS-6) per Response Assessment in Neuro-Oncology Working Group criteria; secondary end points included response rate, overall survival (OS), and safety/tolerability. RESULTS: Fifty-six patients received MEDI-575. Median age was 56.5 years (range, 23-79), 66% of patients were male, 66% were aged ≥65 years, and 46% and 55% had baseline ECOG performance status 0 and 1, respectively. PFS-6 was 15.4% (90% confidence interval: 8.1-24.9). No complete or partial responses were observed; 23 (41%) patients had stable disease as their best response. Median PFS was 1.4 months (90% CI: 1.4-1.8); median OS was 9.7 months (90% CI: 6.5-11.8). No dose-limiting toxicities were observed. The most common treatment-related adverse events (AEs) were diarrhea (16%), nausea (13%), fatigue (13%), tinnitus (4%), asthenia (4%), and dizziness (4%). Seventeen (30%) patients experienced serious AEs, including convulsion (9%), hydrocephalus (5%), pneumonia (4%), and fall (4%); only headache, somnolence, and fall (all in 1 patient) were considered treatment-related. Seven patients (13%) discontinued MEDI-575 due to adverse events. Thirty patients died during the study; no death was considered related to MEDI-575 treatment. CONCLUSIONS: MEDI-575 was well tolerated, with no dose-limiting toxicities. MEDI-575 had similar PFS-6 rates versus historical patients treated with chemotherapy.
Source: Neuro-Oncology
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2338595463